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Licensed Unlicensed Requires Authentication Published by De Gruyter April 18, 2023

Bioavailability of the tumor necrosis factor alpha/regulated on activation, normal T cell expressed and secreted (RANTES) biosystem inside the gestational sac during the pre-immune stages of embryo development

  • Jacobo L. Santolaya EMAIL logo , David S. Schweer , Joel Cardenas-Goicoechea , Radek Bukowski and Joaquin Santolaya-Forgas

Abstract

Objectives

In-vivo studies of the bioavailability of major components of the tumor necrosis factor alpha (TNFα) biosystem inside the gestational sac during embryogenesis have not been reported. We sought to determine the concentration of TNFα, soluble (s) TNFα receptors (sTNFR1, sTNFR2), and RANTES in the primate extraembryonic celomic fluid (ECF).

Methods

A validated timed-pregnant baboon animal model (N: 10) for experimental research in pregnancy was used to collect paired maternal blood and ECF samples in ongoing pregnancies. The concentrations (pg/dL) of TNFα, sTNFR1, sTNFR2, and RANTES were then determined by ELISA immunoassays.

Results

All animals delivered at term healthy newborns. The differential concentration of TNFα, sTNFR1, sTNFR2, and RANTES between the maternal plasma and the ECF could be determined with ratios for TNFα (5.4), sTNFR2 (1.85) and RANTES (3.59) that contrasted with that of sTNFR1 (0.07), which favored the gestational sac compartment. No significant correlations were noted between maternal plasma and ECF TNFR1, sTNFR2 and RANTES. There was a trend for a correlation between TNFα in maternal plasma and ECF (R=0.74; p=0.07).

Conclusions

We report the physiological concentrations of TNFα, sTNFR1, sTNFR2, and RANTES in extraembryonic celomic fluid during embryogenesis in primates.


Corresponding author: Jacobo L. Santolaya, MD, Assistant Professor of Pediatrics, Division of Pediatric Gastroenterology, Department of Pediatrics, University of Texas Southwestern Medical Center, 1935 Medical District Drive, Dallas, TX 75235, USA, E-mail:

Funding source: Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI

Funding source: The Laura Bush Women’s Health Research Institute at Texas Tech Health Science Center

Acknowledgments

The authors are grateful to Dr. Roberto Romero, Dr. Sam Edwin and staff at the Hutzel Women’s Hospital and the Perinatology Research Branch, NICHD/NIH/DHHS Laboratories for validating, performing and reporting the results of the Immunoassays. The authors also recognize Dr. Roman Wolf, at the Biological Resource Laboratory at the Oklahoma University, for his professional and technical help handling the animals and samples.

  1. Research funding: The study was supported by the Laura Bush Women’s Health Research Institute at Texas Tech Health Science Center and the Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. JLS, JCG and RB participated in the writing, interpretation of the data and in the final approval of the manuscript. JLS, DS performed literature reviews and prepared the manuscript cooperatively. JSF performed all the ultrasound-guided celocentesis, was responsible for the study design, drafted and critically revised the manuscript. All authors read and approved the final manuscript.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: The Oklahoma University Animal Care Committee approved the research protocol. The American Association for Accreditation of Laboratory Animal Care accredited the facilities at Oklahoma University.

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Received: 2022-11-09
Accepted: 2023-03-06
Published Online: 2023-04-18
Published in Print: 2023-09-26

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